The K (capsular or envelope) antigens of Enterobacteriaceae lie exterior to the trilamellar outer membrane and have been implicated in the pathogenicity and invasiveness of Escherichia coli and Klebsiella. Only one E. coli K antigen (K-1), however, is accepted as a viruience factor in septicemic human disease (neonatal meningitis), and there is little information on the K types causing nosocomial gram-negative bacillemia and the protective role of anti-K antibodies. We have observed that 40% of all bacteremic E. coli and 80% of K-1 strains are resistant to phagocytosis even in normal serum. For K-1 the mechanism of "resistance" is restricted alternative pathway complement activation. Major goals of this study include: (1) Continued screening of blood isolates for phagocytic resistance and establishing clinical correlates, (2) immunochemical preparation of additional K antigens, particularly from "resistant" strains, (3) determining the mechanism of phagocytic resistance in non-K-1 strains of defined O and K type by evaluating polysaccharide content and complement activation, (4) establishing improved methods for K-typing and screening "resistant" isolates for new types, (5) developing immunoassays for antigen detection and quantitation of K-antibodies, thereby facilitating study of their protective role, (6) antigen modification to improve immunogenicity. Because some K antigens cross-react with antigens of Streptococcus pneumoniae, investigation of cross-reacting antibodies in in vitro phagocytosis tests may suggest the potential protective impact of pneumococcal immunization on some types of gram-negative rod septicemia. Study of the phenomena of resistance to phagocytosis of K types may provide insight into the pathogenesis of many commonly occurring gram-negative bacillary infections and rational approaches to their control by immunoprophylaxis.